The biology of senescence: potential for prevention of disease

A recent series of advances in the understanding of mechanisms responsible for senescence have opened up potential avenues for delaying its onset and that of associated chronic diseases. Because the onset of senescence, like other biological processes, appears to be subject to regulation, advantage is being taken of pathways involved in this regulation to develop therapeutic interventions. These pathways include: (1) development of nutritional interventions based on the finding that caloric restriction extends maximum life span; (2) drugs to influence the metabolic pathways that link effects of caloric restriction to the changes in gene regulation that occur with aging; (3) drugs to prevent formation of advanced glycation end products resulting from reaction of reducing sugars with macromolecules; (4) agents to slow damaging effects of reactive oxygen species; and (5) methods to overcome effects of telomere shortening. Interventions to correct age-related, tissue specific changes in expression of transcription factors that enable cells to acquire specialized function are already in use (e.g., thiazolidinediones). In addition, because the aging process can be reset by factors present in oocytes, as shown by the cloning of healthy animals from senescent cells, methods to rejuvenate cells for transplantation or even intact tissues in individuals are within the realm of possibility. The hope in developing these interventions is to push back the onset of the chronic diseases associated with senescence and to prolong the period of adult vigor.